Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase.

Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

Cooler and drier conditions increase parasitism in a subtropical damselfly population.

Host-parasite interactions are impacted by climate, which may result in variation of parasitism across landscapes and time. Understanding how parasitism varies across these spatio-temporal scales is crucial to predicting how organisms will respond to and cope under a rapidly changing climate. Empirical work on how parasitism varies across climates is limited. Here, we examine the variation of parasitism across seasons and identify the likely climatic factors that explain this variation using Agriocnemis femina damselflies and Arrenurus water mite ectoparasites as a host-parasite study system. We assessed parasitism in a natural population in Sylhet, Bangladesh which is located in subtropical climate between 2021 and 2023. We calculated prevalence (proportion of infected individuals) and intensity (the number of parasites on an infected individual) of parasitism across different seasons. Parasite prevalence and intensity were greater during cooler seasons (autumn and winter) compared to hotter seasons (spring and summer). Mean temperature and precipitation were negatively correlated with parasite prevalence, whereas only mean precipitation was negatively correlated with parasite intensity. Tropical, subtropical and mediterranean regions are predicted to experience extreme climatic events (extreme temperature, less precipitation and frequent drought) as a consequence of anthropogenic climate change, and our finding suggests that this might alter patterns of parasitism in aquatic insects.